chr10-33263767-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_003873.7(NRP1):​c.537G>A​(p.Val179Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,612,932 control chromosomes in the GnomAD database, including 28,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.21 ( 3776 hom., cov: 32)
Exomes 𝑓: 0.18 ( 25137 hom. )

Consequence

NRP1
NM_003873.7 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0240
Variant links:
Genes affected
NRP1 (HGNC:8004): (neuropilin 1) This gene encodes one of two neuropilins, which contain specific protein domains which allow them to participate in several different types of signaling pathways that control cell migration. Neuropilins contain a large N-terminal extracellular domain, made up of complement-binding, coagulation factor V/VIII, and meprin domains. These proteins also contains a short membrane-spanning domain and a small cytoplasmic domain. Neuropilins bind many ligands and various types of co-receptors; they affect cell survival, migration, and attraction. Some of the ligands and co-receptors bound by neuropilins are vascular endothelial growth factor (VEGF) and semaphorin family members. This protein has also been determined to act as a co-receptor for SARS-CoV-2 (which causes COVID-19) to infect host cells. [provided by RefSeq, Nov 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 10-33263767-C-T is Benign according to our data. Variant chr10-33263767-C-T is described in ClinVar as [Benign]. Clinvar id is 3059652.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.024 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NRP1NM_003873.7 linkuse as main transcriptc.537G>A p.Val179Val synonymous_variant 4/17 ENST00000374867.7 NP_003864.5 O14786-1Q68DN3Q59F20Q6AWA9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NRP1ENST00000374867.7 linkuse as main transcriptc.537G>A p.Val179Val synonymous_variant 4/171 NM_003873.7 ENSP00000364001.2 O14786-1

Frequencies

GnomAD3 genomes
AF:
0.212
AC:
32222
AN:
151816
Hom.:
3776
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.291
Gnomad AMI
AF:
0.355
Gnomad AMR
AF:
0.176
Gnomad ASJ
AF:
0.165
Gnomad EAS
AF:
0.472
Gnomad SAS
AF:
0.200
Gnomad FIN
AF:
0.175
Gnomad MID
AF:
0.104
Gnomad NFE
AF:
0.161
Gnomad OTH
AF:
0.200
GnomAD3 exomes
AF:
0.201
AC:
50578
AN:
251416
Hom.:
6029
AF XY:
0.197
AC XY:
26739
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.298
Gnomad AMR exome
AF:
0.181
Gnomad ASJ exome
AF:
0.166
Gnomad EAS exome
AF:
0.472
Gnomad SAS exome
AF:
0.188
Gnomad FIN exome
AF:
0.166
Gnomad NFE exome
AF:
0.164
Gnomad OTH exome
AF:
0.183
GnomAD4 exome
AF:
0.177
AC:
259191
AN:
1460996
Hom.:
25137
Cov.:
32
AF XY:
0.177
AC XY:
128723
AN XY:
726892
show subpopulations
Gnomad4 AFR exome
AF:
0.299
Gnomad4 AMR exome
AF:
0.180
Gnomad4 ASJ exome
AF:
0.164
Gnomad4 EAS exome
AF:
0.442
Gnomad4 SAS exome
AF:
0.187
Gnomad4 FIN exome
AF:
0.162
Gnomad4 NFE exome
AF:
0.164
Gnomad4 OTH exome
AF:
0.191
GnomAD4 genome
AF:
0.212
AC:
32259
AN:
151936
Hom.:
3776
Cov.:
32
AF XY:
0.214
AC XY:
15858
AN XY:
74234
show subpopulations
Gnomad4 AFR
AF:
0.291
Gnomad4 AMR
AF:
0.176
Gnomad4 ASJ
AF:
0.165
Gnomad4 EAS
AF:
0.470
Gnomad4 SAS
AF:
0.200
Gnomad4 FIN
AF:
0.175
Gnomad4 NFE
AF:
0.161
Gnomad4 OTH
AF:
0.201
Alfa
AF:
0.170
Hom.:
3554
Bravo
AF:
0.218
Asia WGS
AF:
0.332
AC:
1153
AN:
3478
EpiCase
AF:
0.164
EpiControl
AF:
0.158

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

NRP1-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 01, 2022This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.78
DANN
Benign
0.61
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2070296; hg19: chr10-33552695; COSMIC: COSV55162348; COSMIC: COSV55162348; API